6. Molecular Basis of Inheritance
The Molecular Basis of Inheritance
Central Dogma: Proposed by Watson and Crick, explaining the flow of genetic information:
DNA can replicate itself (DNA polymerase facilitates this).
Transcription: DNA is transcribed into RNA.
Translation: RNA is translated into proteins.
No mechanism exists for proteins to revert back to RNA.
DNA makes proteins, which carry out functions in the cell.
Evidence of DNA as Transforming Factor (Frederick Griffith's Experiment):
Mice injected with a mix of heat-killed S strain and live R strain bacteria died, indicating genetic transformation.
Transformation:
A change in genotype and phenotype resulting from the assimilation of external DNA by a cell.
Example: antibiotic resistance due to bacteria incorporating new DNA.
Viral DNA Programs Cells (Bacteriophages):
Bacteriophages are viruses that infect bacteria.
Viruses are simpler than cells; they consist of DNA or RNA enclosed by a capsid (protective protein coat).
Viruses infect cells and take over the cell's metabolic machinery to reproduce.
The virus inserts its DNA/RNA into the host DNA system, exploiting the host's replication mechanisms to produce more viral components.
These components assemble, and the cycle repeats.
Hershey-Chase Experiment:
Radioactive sulfur (tagged proteins) was found in the supernatant.
Radioactive phosphorus (tagged DNA) was found in the pellet.
Conclusion: DNA is the genetic material.
DNA Structure:
DNA is a polymer of nucleotides.
Each nucleotide consists of: a nitrogenous base, a pentose sugar (deoxyribose), and a phosphate group.
Chargaff's Rules:
The number of purines equals the number of pyrimidines.
Purines: Adenine (A) and Guanine (G). Pyrimidines: Cytosine (C) and Thymine (T).
and
DNA Double Helix:
DNA is a double helix with two antiparallel strands.
The sugar-phosphate backbone is on the outside, while the nitrogenous bases are on the inside.
RNA is typically a single helix.
DNA Replication: Semiconservative Model:
The original information encoded in each parental strand is conserved in the daughter molecule.
Each new DNA molecule consists of one original (old) strand and one newly synthesized strand.
DNA Replication Mechanism
Origins of Replication: DNA replication always starts at origins of replication, forming a replication bubble.
Helicase: Unwinds the DNA double helix, separating the two strands.
Single-Stranded Binding Proteins: Prevent the separated DNA strands from re-annealing (binding back together).
qPrimase: Synthesizes RNA primers, which initiate DNA synthesis by DNA polymerase.
DNA Polymerase: Adds nucleotides to the 3' end of the growing DNA strand.
Leading Strand: Synthesized continuously in the 5' to 3' direction.
Lagging Strand: Synthesized discontinuously in the 5' to 3' direction, forming Okazaki fragments.
Okazaki Fragments: Short sequences of DNA synthesized on the lagging strand.
Telomere Replication
Telomeres: Extensions of the original chromosome that protect DNA from degradation.
As the body ages, the mechanism to protect the telomeres fail.
Chargaff's Rules:
The number of purines equals the number of pyrimidines.
Purines: Adenine (A) and Guanine (G). Pyrimidines: Cytosine (C) and Thymine (T).
and
Purines are larger, two-ring molecules, while pyrimidines are smaller, single-ring molecules. Because purines always pair with pyrimidines, the structure of DNA remains consistent.
DNA Replication Mechanism
Origins of Replication: DNA replication always starts at origins of replication, forming a replication bubble.
DNA molecule separates at specific locations, called origins of replication, creating replication bubbles.Helicase: Unwinds the DNA double helix, separating the two strands.
Helicase enzymes bind to the replication origin and unwind the double helix structure by breaking the hydrogen bonds between the base pairs. This action causes the DNA to separate into two single strands, forming a replication fork.Single-Stranded Binding Proteins: Prevent the separated DNA strands from re-annealing (binding back together).
Single-stranded binding proteins (SSBPs) attach to each strand of DNA to stabilize them and prevent them from re-forming the double helix. These proteins ensure that each strand remains accessible for the DNA polymerase to use as a template.Primase: Synthesizes RNA primers, which initiate DNA synthesis by DNA polymerase.
An enzyme called primase synthesizes short RNA sequences known as primers. These primers are essential because DNA polymerase can only add nucleotides to an existing strand. The RNA primer provides this starting point.DNA Polymerase: Adds nucleotides to the 3' end of the growing DNA strand.
DNA polymerase is the primary enzyme involved in DNA replication. It adds nucleotides to the 3' end of the primer, extending the new DNA strand. DNA polymerase also checks for errors and corrects them, ensuring high fidelity in DNA replication.Leading Strand: Synthesized continuously in the 5' to 3' direction.
The leading strand is synthesized continuously from a single primer. DNA polymerase moves along the strand from the 5' to the 3' end, adding complementary nucleotides as it goes.Lagging Strand: Synthesized discontinuously in the 5' to 3' direction, forming Okazaki fragments.
The lagging strand is synthesized discontinuously because DNA polymerase can only add nucleotides to the 3' end, and the lagging strand runs in the opposite direction. It is synthesized in short fragments.Okazaki Fragments: Short sequences of DNA synthesized on the lagging strand.
Okazaki fragments are short DNA fragments synthesized on the lagging strand. Each Okazaki fragment requires a separate RNA primer. After DNA polymerase extends these fragments, another enzyme removes the RNA primers and replaces them with DNA. DNA ligase then seals the gaps between the Okazaki fragments, creating a continuous strand of DNA.